National Engineering Research Center for Biomaterials, Sichuan University, Chengdu 610064, China.
Institute of Polymers, Composites and Biomaterials (IPCB)-National Research Council of Italy (CNR), 80125 Naples, Italy.
ACS Appl Mater Interfaces. 2020 Aug 26;12(34):37873-37884. doi: 10.1021/acsami.0c09004. Epub 2020 Aug 13.
Injectable biphasic calcium phosphates have been proposed as a solution in the treatment of a range of clinical applications including as fillers in the augmentation of osteoporotic bone. To date, various biodegradable natural or synthetic organics have been used as a polymer component of bone materials to increase their cohesiveness. Herein, a novel bone material was developed combining osteoconductive biphasic calcium phosphate (BCP) nanoparticles with phosphoserine-tethered generation 3 poly(epsilon-lysine) dendron (G3-K PS), a class of hyperbranched peptides previously shown to induce biomineralization and stem cell osteogenic differentiation. Strontium was also incorporated into the BCP nanocrystals (SrBCP) to prevent bone resorption. Within 24 h, an antiwashout behavior was observed in G3-K PS-integrated pure BCP group (BCPG3). Moreover, both in vitro tests by relevant cell phenotypes and an in vivo tissue regeneration study by an osteoporotic animal bone implantation showed that the integration of G3-K PS would downregulate Cxcl9 gene and protein expressions, thus enhancing bone regeneration measured as bone mineral density, new bone volume ratio, and trabecular microarchitectural parameters. However, no synergistic effect was found when Sr was incorporated into the BCPG3 bone pastes. Notably, results indicated a concomitant reduction of bone regeneration potential assessed as reduced Runx2 and PINP expression when bone resorptive RANKL and CTX-I levels were reduced by Sr supplementation. Altogether, the results suggest the potential of injectable BCPG3 bone materials in the treatment of osteoporotic bone defects.
可注射双相磷酸钙已被提议作为一种解决方案，用于治疗多种临床应用，包括作为骨质疏松性骨增强的填充物。迄今为止，各种可生物降解的天然或合成有机物已被用作骨材料的聚合物成分，以增加其内聚性。在此，开发了一种新型骨材料，将骨诱导性双相磷酸钙（BCP）纳米颗粒与磷酸丝氨酸键合的第三代聚（ε-赖氨酸）树枝状大分子（G3-K PS）结合，G3-K PS 是一类先前已显示可诱导生物矿化和干细胞成骨分化的超支肽。还将锶掺入 BCP 纳米晶体（SrBCP）中以防止骨吸收。在 24 小时内，观察到 G3-K PS 整合的纯 BCP 组（BCPG3）中出现抗洗脱行为。此外，通过相关细胞表型的体外测试和骨质疏松动物骨植入的体内组织再生研究表明，G3-K PS 的整合会下调 Cxcl9 基因和蛋白表达，从而增强骨再生，如骨矿物质密度、新骨体积比和小梁微观结构参数。然而，当 Sr 掺入 BCPG3 骨糊剂中时，没有发现协同作用。值得注意的是，结果表明，当通过 Sr 补充降低骨吸收 RANKL 和 CTX-I 水平时，作为骨再生潜在性评估的 Runx2 和 PINP 表达降低，同时降低了骨再生的潜力。总的来说，这些结果表明可注射 BCPG3 骨材料在治疗骨质疏松性骨缺损方面具有潜力。
